The paroxysmal depolarization shift (PDS) represents the most typical and consistent intracellular correlate of an epileptogenic lesion produced by penicillin topically applied to the cerebral cortex. Investigations dealing with the origin and mechanisms underlying the PDS have failed to demonstrate a factor that would uniquely explain observed phenomena. Testing of impaled neurons during the inter-PDS interval has demonstrated no abnormalities and it is becoming generally accepted that the mechanism underlying the PDS is presynaptic in origin. The present investigation proposes to observe the "spontaneous" miniature postsynaptic potentials (MPSPs) of normal and penicillin treated cortical neurons. Under the presumption that the MPSPs will reflect the net effects of transmitter release and presynaptic membrane integrity, if as indicated the postsynaptic membrane is normal. Furthermore, since the development of the PDS appears to be impulse- dependent, any differential alterations of the impulse-dependent and/or non-impulse-dependent MPSPs would be of significance. Studies to date suggest that the impulse dependent MPSPs are diminished in amplitude while the others are unaffected. Further investigation is intended to confirm the initial observations and to determine the significance of presumed presynaptic terminal depolarization in regard to the generation of the PDS and finally to describe the presynaptic mechanism involved.